Doped-type metal sulfide phosphor nanoparticle, dispersion thereof, and method for producing the same

ABSTRACT

A doped-type metal sulfide phosphor nanoparticle dispersion, comprising a doped-type metal sulfide phosphor nanoparticle dispersed in water and/or a hydrophilic solvent, wherein the doped-type metal sulfide phosphor nanoparticle comprises a surface that is modified with a surface modifier, the surface modifier being a compound represented by formula [I]: 
 
HS-L-W   Formula [I]
 
wherein L represents a divalent linking group; and W represents COOM or NH 2 , in which M represents a hydrogen atom, an alkali metal atom, or NX 4 , in which X represents a hydrogen atom or an alkyl group.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a divisional of Application No. 10/982,876, filedNov. 8, 2004, the contents of which being incorporated herein byreference, which in turn claims the benefit of foreign priority ofJapanese Application Nos. 2003-380437 and 2004-052021, filed Nov. 10,2003, and Feb. 26, 2004, respectively.

FIELD OF THE INVENTION

The present invention relates to a doped-type metal sulfide phosphornanoparticle which is applicable, for example, to afluorescently-labeling material and a luminescent device; a dispersionthereof; and a method for producing the nanoparticle or of thedispersion.

BACKGROUND OF THE INVENTION

It is known that a nanometer-size particulate material can exhibitproperties distinct from those of the corresponding bulk material. Forexample, a semiconductor is well known for the so-called quantum sizeeffect, in which the band gap, which had been believed to bematerial-specific, varies with particle size. The particle size at whichthis effect is significant is generally from a few nm to tens of nm,depending on the type of semiconductor material. Thus, asinglenanoparticle is particularly important. Some materials are alsoknown for another effect, in which, as the quantum size effect becomessignificant, the fluorescence lifetime becomes short, and a certainluminescence becomes to be observed, which would otherwise not beobserved. As mentioned above, nanosized materials, in particularsingle-nanosized materials, can exhibit properties different from theknown properties of the corresponding bulk materials, and thus areattracting widespread attention in science and engineering.

A certain semiconductor nanoparticle phosphor material is proposed thatcomprises a semiconductor nanoparticle, for example, of CdSe/CdS(core/shell), CdSe/ZnS (core/shell), or the like, and the semiconductornanoparticle is utilized to form beads whose surface is coupled to amolecule probe for detecting a target molecule (see, for example,Science, Vol. 281, No. 25, 1998, pp. 2013-2016, and NatureBiotechnology, Vol. 19, 2001, pp. 631-6354). These semiconductornanoparticles of different crystallite sizes can produce differentwavelengths of emission. If the labeled beads are encoded with respectto a combination of luminescence wavelength and luminescence intensity,simultaneous multiple measurements are possible. The semiconductornanoparticle phosphor material has good properties for a labelingmaterial, such as high sensitivity, low cost, and easiness ofautomation. Using the semiconductor nanoparticle phosphor material as alabeling material, therefore, a specific site of a living organism, acertain substance in plasma, or the like, can be detected at highsensitivity and high speed.

Another semiconductor nanoparticle phosphor material is proposed thatcomprises a semiconductor nanoparticle whose surface is coated with amodifying molecule, so as to have improved affinity to the matrix (forexample, see U.S. Pat. No. 6,319,426, JP-A-2002-38145 (“JP-A” meansunexamined published Japanese patent application), JP-A-2003-64278; andScience, Vol. 281, No. 25, 1998, pp. 2016-2018). The semiconductornanoparticle coated with the modifying molecule can have improvedaffinity to an aqueous medium, and/or improved dispersibility in anorganic macromolecule or an organic solvent. Thus, the semiconductornanoparticle phosphor material can easily be applied as a labelingmaterial, and a luminescent material can easily be produced bydispersing the semiconductor nanoparticle phosphor material into aresin. The semiconductor nanoparticle phosphor material is thereforeexpected to be widely applied in the fields of optical devices, clinicaldiagnosis, biochemical research or medical science research, or thelike.

However, the use of the semiconductor nanoparticle phosphor material ofCdSe or CdSe/ZnS (core/shell) or the like may raise safety issues andenvironmental issues. Therefore, alternatives are desired that are safeand have less influence on the environment. A useful alternative is ananoparticle phosphor material of zinc sulfide (ZnS) doped withmanganese ion (Mn²⁺) or the like, which material can easily besynthesized in a solvent, such as water. Compared with the case of theabove semiconductor nanoparticle phosphor material, it is difficult tocontrol the luminescence wavelength of the zinc sulfide (ZnS)nanoparticle phosphor material by varying its crystallite size. On theother hand, the ZnS nanoparticle phosphor material is advantageous inthat its luminescence wavelength can be varied with the type of thedoping metal ion or the surface-modifying molecule (surface modifier)(for example, see JP-A-2002-322468; Journal of the IlluminatingEngineering Institute of Japan, Vol. 87, No. 4, 2003, pp. 256-261; andJournal of The Electrochemical Society, Vol. 149, No. 3, 2002, pp.H72-H75).

However, the zinc sulfide (ZnS)-based nanoparticle phosphor material hasa relatively large surface area, such that it can significantly causesecondary aggregation, thus the zinc sulfide (ZnS)-based nanoparticlephosphor material cannot easily form a transparent colloidal dispersion,and it can hardly be functionalized for the purpose of application tofluorescent labeling materials or luminescent devices. JP-A-2002-38145discloses ZnS-based nanoparticles having a specific aminogroup-containing compound fixed on the surface by condensation reaction.However, it has been found that such a compound does not always havesufficient dispersibility in a specific solvent, such as water.

SUMMARY OF THE INVENTION

The present invention resides in a doped-type metal sulfide phosphornanoparticle, whose surface is modified with a surface modifier, thesurface modifier being a compound represented by formula [I]:HS-L-W   Formula [I]wherein L represents a divalent linking group; and W represents COOM orNH₂, in which M represents a hydrogen atom, an alkali metal atom, orNX₄, in which X represents a hydrogen atom or an alkyl group.

Further, the present invention resides in a doped-type metal sulfidephosphor nanoparticle dispersion, wherein the doped-type metal sulfidephosphor nanoparticle is dispersed in water and/or a hydrophilicsolvent.

Further, the present invention resides in a doped-type metal sulfidephosphor nanoparticle dispersion, wherein the doped-type metal sulfidephosphor nanoparticle is dispersed in a hydrophobic organic solvent.

Further, the present invention resides in a method of producing adoped-type metal sulfide phosphor nanoparticle whose surface is modifiedwith a surface modifier, which comprises the steps of:

carrying out a reaction of a doping metal ion and a matrix metal ion,with a sulfide ion, in water and/or a hydrophilic solvent by acoprecipitation method; and

adding thereto a surface modifier comprising the compound represented byformula [I].

Further, the present invention resides in a method of producing adispersion of a doped-type metal sulfide phosphor nanoparticle whosesurface is modified with a surface modifier, which comprises the stepsof:

carrying out a reaction of a doping metal ion and a matrix metal ion,with a sulfide ion, in water and/or a hydrophilic solvent by acoprecipitation method; and

adding thereto a surface modifier comprising the compound represented byformula [I].

Further, the present invention resides in a method of producing adispersion of a doped-type metal sulfide phosphor nanoparticle, whichcomprises the steps of:

carrying out a reaction of a doping metal ion and a matrix metal ion,with a sulfide ion, in the presence of a nitrogen-containingheterocyclic compound in water and/or a hydrophilic solvent; and

adding thereto the compound represented by formula [I].

Further, the present invention resides in a method of producing adispersion of a doped-type metal sulfide phosphor nanoparticle, whichcomprises the steps of:

carrying out a reaction of a doping metal ion and a matrix metal ion,with a sulfide ion, by a reverse micelle method in a non-water solubleorganic solvent containing a trace amount of water;

adding thereto the compound represented by formula [I]; and

adding a good solvent for the compound represented by formula [I], toperform re-dispersion.

Further, the present invention resides in a fluorescent-labelingmaterial, wherein an affinity molecule is coupled to the doped-typemetal sulfide phosphor nanoparticle.

Further, the present invention resides in a method of producing afluorescent-labeling material, which comprises the step of:

coupling an affinity molecule, to a terminal group of the surfacemodifier which covers the doped-type metal sulfide phosphornanoparticle.

Other and further features and advantages of the invention will appearmore fully from the following description.

DETAILED DESCRIPTION OF THE INVENTION

According to the present invention, there are provided the followingmeans:

-   (1) A doped-type metal sulfide phosphor nanoparticle, whose surface    is modified with a surface modifier, the surface modifier being a    compound represented by formula [I]:    HS-L-W   Formula [I]    wherein L represents a divalent linking group; and W represents COOM    or NH₂, in which M represents a hydrogen atom, an alkali metal atom,    or NX₄, in which X represents a hydrogen atom or an alkyl group;-   (2) The doped-type metal sulfide phosphor nanoparticle according to    the above item (1), wherein the metal sulfide is zinc sulfide;-   (3) A doped-type metal sulfide phosphor nanoparticle dispersion,    wherein the doped-type metal sulfide phosphor nanoparticle according    to the above item (1) or (2) is dispersed in water and/or a    hydrophilic solvent;-   (4) The doped-type metal sulfide phosphor nanoparticle dispersion    according to the above item (3), containing a nitrogen-containing    heterocyclic compound in the dispersion;-   (5) A doped-type metal sulfide phosphor nanoparticle dispersion,    wherein the doped-type metal sulfide phosphor nanoparticle according    to the above item (1) or (2) is dispersed in a hydrophobic organic    solvent;-   (6) A method of producing a doped-type metal sulfide phosphor    nanoparticle whose surface is modified with a surface modifier,    comprising the steps of:

carrying out a reaction of a doping metal ion and a matrix metal ion,with a sulfide ion, in water and/or a hydrophilic solvent by acoprecipitation method; and

adding thereto a surface modifier comprising a compound represented byformula [I]:HS-L-W   Formula [I]wherein L represents a divalent linking group; and W represents COOM orNH₂, in which M represents a hydrogen atom, an alkali metal atom, orNX₄, in which X represents a hydrogen atom or an alkyl group;

-   (7) The method of producing a doped-type metal sulfide phosphor    nanoparticle according to the above item (6), wherein the reaction    is carried out under conditions that the total number of moles of    the doping metal ion and the matrix metal ion is greater than the    number of moles of the sulfide ion; (8) The method of producing a    doped-type metal sulfide phosphor nanoparticle according to the    above item (6) or (7), comprising the step of: performing    purification by centrifugal separation, after adding the compound    represented by formula [I];-   (9) The method of producing a doped-type metal sulfide phosphor    nanoparticle according to the above item (6) or (7), comprising the    step of: performing purification by ultrafiltration, after adding    the compound represented by formula [I];-   (10) The method of producing a doped-type metal sulfide phosphor    nanoparticle according to any one of the above items (6) to (9),    comprising the step of: performing freeze-drying or vacuum-drying;-   (11) A method of producing a dispersion of a doped-type metal    sulfide phosphor nanoparticle whose surface is modified with a    surface modifier, comprising the steps of:

carrying out a reaction of a doping metal ion and a matrix metal ion,with a sulfide ion, in water and/or a hydrophilic solvent by acoprecipitation method; and

adding thereto a surface modifier comprising a compound represented byformula [I]:HS-L-W   Formula [I]wherein L represents a divalent linking group; and W represents COOM orNH₂, in which M represents a hydrogen atom, an alkali metal atom, orNX₄, in which X represents a hydrogen atom or an alkyl group;

-   (12) A method of producing a dispersion of a doped-type metal    sulfide phosphor nanoparticle, comprising the steps of:

carrying out a reaction of a doping metal ion and a matrix metal ion,with a sulfide ion, in the presence of a nitrogen-containingheterocyclic compound in water and/or a hydrophilic solvent; and

adding thereto a compound represented by formula [I]:HS-L-W   Formula [I]wherein L represents a divalent linking group; and W represents COOM orNH₂, in which M represents a hydrogen atom, an alkali metal atom, orNX₄, in which X represents a hydrogen atom or an alkyl group;

-   (13) A method of producing a dispersion of a doped-type metal    sulfide phosphor nanoparticle, comprising the steps of:

carrying out a reaction of a doping metal ion and a matrix metal ion,with a sulfide ion, by a reverse micelle method in a non-water solubleorganic solvent containing a trace amount of water;

adding thereto a compound represented by formula [I]; and

adding a good solvent for the compound represented by formula [I], toperform re-dispersion:HS-L-W   Formula [I]wherein L represents a divalent linking group; and W represents COOM orNH₂, in which M represents a hydrogen atom, an alkali metal atom, orNX₄, in which X represents a hydrogen atom or an alkyl group;

-   (14) The method of producing a dispersion of a doped-type metal    sulfide phosphor nanoparticle according to any one of the above    items (11) to (13), wherein the reaction is carried out under    conditions that the total number of moles of the doping metal ion    and the matrix metal ion is greater than the number of moles of the    sulfide ion;-   (15) The method of producing a dispersion of a doped-type metal    sulfide phosphor nanoparticle according to any one of the above    items (11) to (14), comprising the step of: performing purification    by centrifugal separation;-   (16) The method of producing a dispersion of a doped-type metal    sulfide phosphor nanoparticle according to any one of the above    items (11).to (14), comprising the step of: performing purification    by ultrafiltration;-   (17) A fluorescent-labeling material, wherein an affinity molecule    is coupled to the doped-type metal sulfide phosphor nanoparticle    according to the above item (1) or (2); and-   (18) A method of producing a fluorescent-labeling material,    comprising the step of:

coupling an affinity molecule, to a terminal group of the surfacemodifier which covers the doped-type metal sulfide phosphor nanoparticleaccording to the above item (1) or (2).

The present invention is described in detail below.

As a result of active investigations in view of the above problems inthe conventional techniques, the inventors of the present invention havefound that, when the compound represented by formula [I] is used as asurface modifier, well-dispersible metal sulfide nanoparticle materialscan be obtained, and that zinc sulfide-based nanoparticle phosphormaterials can be obtained that have high sensitivity and uniformluminescent properties and can easily be functionalized. The presentinvention has been attained based on these findings.

[l] Surface Modifier

According to the present invention, the dispersibility of a collectionof metal sulfide nanoparticles in a solvent can be improved, using thesurface modifier of the compound represented by formula [I] (hereinafteralso referred to as the surface modifier for use in the presentinvention). Using the surface modifier also produces the advantage thata molecule probe for detecting a target molecule can easily be coupledthereto.HS-L-W   Formula [I]

In the formula, L represents a divalent linking group, and W representsCOOM or NH₂, wherein M represents a hydrogen atom, an alkali metal atom,or NX₄, wherein X represents a hydrogen atom or an alkyl group.

Examples of the linking group include an alkylene group (e.g. achain-like or cyclic alkylene group having generally 1 to 20 carbonatoms, preferably 1 to 18 carbon atoms, such as methylene, ethylene,trimethylene, tetramethylene, hexamethylene, propylene, ethylethylene,and cyclohexylene).

The linking group may have an unsaturated bond. Examples of such anunsaturated group include an alkenylene group (e.g. a chain-like orcyclic alkenylene group having generally 1 to 20 carbon atoms,preferably 1 to 18 carbon atoms, such as vinylene, propenylene,1-butenylene, 2-butenylene, 2-pentenylene, 8-hexadecenylene,1,3-butanedienylene, and cyclohexenylene), an alkynylene group (e.g. analkynylene group having generally 1 to 20 carbon atoms, preferably 1 to18 carbon atoms, such as ethynylene and propynylene), and an arylenegroup (e.g. an arylene group having generally 6 to 14 carbon atoms, suchas phenylene, naphthylene and anthrylene, preferably a phenylene groupof 6 carbon atoms).

The linking group may have at least one hetero atom (the hetero atommeans any atom other than a carbon atom, e.g. a nitrogen atom, an oxygenatom and a sulfur atom). The hetero atom is preferably an oxygen atom ora sulfur atom, most preferably an oxygen atom. The number of heteroatoms is preferably, but not particularly limited to, at most five, morepreferably at most three.

A partial structure of the linking group may have a functional groupwhich contains a carbon atom adjacent to the hetero atom. Examples ofsuch a functional group include an ester group (including a carboxylategroup, a carbonate group, a sulfonate group, and a sulfinate group), anamido group (including a carboxylic acid amide group, a urethane group,a sulfonic acid amide group, and a sulfinic acid amide group), an ethergroup, a thioether group, a disulfide group, an amino group, and animido group. Any of the above functional groups may also have asubstituent, and L may have a plurality of any of the above functionalgroups. Such plural groups may be the same or different from each other.

The functional group is preferably an ester group, an amido group, anether group, a thioether group, a disulfide group, or an amino group,more preferably an alkenyl group, an ester group, or an ether group.

In the case where W is NH₂, W may form a salt with hydrochloric acid,sulfuric acid, nitric acid, phosphoric acid, sulfonic acid, or the like.The alkali metal atom represented by M may be lithium (Li), sodium (Na),potassium (K), or the like. The alkyl group represented by X may be achain-like alkyl group having generally 1 to 20 carbon atoms, preferably1 to 18 carbon atoms, such as methyl, ethyl, n-propyl, isopropyl,tert-butyl, octyl, and cetyl. The four X groups may be independently anyof the above, and they may be the same or different from each other.

Specific examples of the surface modifier for use in the presentinvention include mercaptoacetic acid, 2-mercaptopropionic acid,3-mercaptopropionic acid, 2-mercaptobutyric acid, 4-mercaptobutyricacid, 8-mercaptooctanoic acid, 11-mercaptoundecanoic acid,18-mercaptostearic acid, 3-mercaptoacrylic acid, mercaptomethacrylicacid, 4-mercaptocrotonic acid, 18-mercaptooleic acid, thiomalic acid,mercaptopropiolic acid, 4-mercaptophenylhydrocinnamic acid,2-mercaptoethylamine, 2-mercaptopropylamine, 3-mercaptopropylamine,3-mercapto-n-butylamine, 4-mercapto-n-butylamine,2-mercapto-tert-butylamine, 8-mercaptooctylamine,11-mercaptoundecylamine, 18-mercaptostearylamine, 18-mercaptooleylamine,5-aminopentanoic acid (2-mercapto-ethyl)-amide, 6-aminohexanoic acid(2-mercapto-ethyl)-amide, 11-aminoundecanoic acid(2-mercapto-ethyl)-amide, 5-aminopentanoic acid-3-mercapto-propyl ester,11-amino-undecanoic acid-3-mercaptopropyl ester,3-(11-amino-undecyloxy)-propane-1-thiol, (2-mercapto-ethylamino)-aceticacid-2-[2-(2-aminoacetoxy)-ethoxy]-ethyl ester. The above aminogroup-containing compound may form a salt with an acid as stated above.These examples are not intended to limit the scope of the presentinvention.

In the case where water is used as the dispersion solvent, the number ofcarbons of L in the surface modifier for use in the present invention ispreferably from 1 to 5, more preferably from 1 to 4. In the case wherean organic solvent is used as the dispersion solvent, the number ofcarbons of L is preferably from 6 to 20, more preferably from 6 to 18.Another surface modifier (e.g. polyethylene glycol, polyoxyethylene (1)lauryl ether phosphate, lauryl ether phosphate, trioctylphosphine,trioctylphosphine oxide, sodium polyphosphate, sodiumbis(2-ethylhexyl)sulfosuccinate, and the like) may coexist during orafter the synthesis of the nanoparticles.

[2] Doped-type Metal Sulfide Phosphor Nanoparticles

Examples of the metal to constitute the doped-type metal sulfidephosphor nanoparticle of the present invention include a Group II metal,e.g. zinc (Zn), cadmium (Cd), and strontium (Sr); preferably zinc (Zn)which is less toxic and can form a relatively stable sulfide in water ora hydrophilic solvent. Examples of the doping activator include metals,e.g. manganese (Mn), copper (Cu), europium (Eu), terbium (Tb), thulium(Tm), aluminum (Al), and silver (Ag), and a compound of any of the abovemetals in combination with chlorine (Cl) or fluorine (F). The dopingactivator does not have to consist of a single type of atom, and it maycomprise different kinds of atoms. The luminescence wavelength may varywith the activator. For example, manganese (Mn)-doped zinc sulfide (ZnS)(hereinafter represented by “ZnS:Mn”) can show an orange luminescence,and europium (Eu)-doped zinc sulfide can show a red luminescence. Theoptimal concentration of the activator is preferably from 0.001 to 10atomic percent, depending on the type of the activator.

The number average particle diameter of the metal sulfide phosphornanoparticle is preferably from 0.5 to 100 nm, more preferably from 0.5to 50 nm, still more preferably from 1 to 10 nm. The particle sizedistribution of the phosphor nanoparticles is preferably from 0 to 50%,more preferably from 0 to 20%, still more preferably from 0 to 10%, interms of coefficient of variation. Herein, the coefficient of variationmeans a percentage value obtained through dividing the arithmeticstandard deviation by the number average particle diameter (arithmeticstandard deviation×100/number average particle diameter).

[3] Methods of Producing a Metal Sulfide Phosphor Nanoparticle and aDispersion Thereof

(1) Coprecipitation Method

The doped-type metal sulfide phosphor nanoparticles may be obtained by aprocess including the steps of: dissolving a salt for the doping metalion and a salt for the matrix metal ion in water and/or a hydrophilicsolvent (e.g. methanol, ethanol, acetonitrile, and tetrahydrofuran), toform a solution; dissolving a sulfide such as sodium sulfide andammonium sulfide in water and/or a hydrophilic solvent, to form anothersolution; and mixing both solutions while stirring them at a high speedby a single-jet method or a double-jet method. The reaction temperatureis generally from 0 to 100° C., preferably from 3 to 80° C.; and thereaction time is generally from one second to 60 minutes, preferably oneminute to 30 minutes. In this process, the synthesis of the metalsulfide phosphor nanoparticles is preferably performed in the presenceof a nitrogen-containing heterocyclic compound so that a colloidaldispersion having good dispersibility can be obtained. Preferredexamples of the nitrogen-containing heterocyclic compound includeimidazoles (such as benzimidazole, 2-hydroxybenzimidazole, and7-hydroxy-5-methylbenzimidazole), indoles (such as 4-hydroxyindole and5-hydroxy-3-methylindole), pyrazoles (such as indazole and5-methyl-1,2-benzopyrazole), and triazoles (such as benzotriazole,1H-benzotriazole-1-methanol, 1H-1,2,3-triazolo[4,5-b]pyridine,3H-1,2,3-triazolo[4,5-b]pyridine-3-ol,7-hydroxy-5-methyl-1,3,4-triazaindolizine, and7-hydroxy-1,2,4-triazolo[4,3-a]pyridine). The addition amount of thenitrogen-containing heterocyclic compound is generally from 0.05 to 100molar times, preferably from 0.1 to 20 molar times the amount of themetal sulfide.

After this process, a dispersion of the metal sulfide phosphornanoparticles may be produced, by adding the surface modifier for use inthe present invention to the reaction product (the surface modifier maybe previously dissolved in water and/or a hydrophilic solvent beforeadded). The addition amount of the surface modifier for use in thepresent invention is generally from 0.05 to 100 molar times, preferablyfrom 0.1 to 20 molar times the amount of the metal sulfide. The amountof the surface modifier coupled to the surface of the particles may varywith the size and concentration of the particles, the type of thesurface modifier (such as size and structure), and the like, but it isgenerally from about 0.005 to about 10 molar times, preferably fromabout 0.01 to about 2 molar times the amount of the metal sulfide.

It is not preferred that the doped-type metal sulfide phosphornanoparticles are synthesized in the presence of the surface modifierfor use in the present invention, because the luminescence intensity maysignificantly be reduced. Therefore, the surface modifier for use in thepresent invention is added after the synthesis of the metal sulfidephosphor nanoparticles.

The doped-type metal sulfide phosphor nanoparticles may be washed andpurified by centrifugation, filtration or the like, and then theresultant particles may be dispersed into a solvent containing thesurface modifier for use in the present invention.

The thus-prepared doped-type metal sulfide phosphor nanoparticledispersion, which contains the surface modifier for use in the presentinvention, may be subjected to repeated centrifugation or decantationwith water and/or a hydrophilic solvent, so that metal sulfide phosphornanoparticles free from salt byproducts and the excessive amount of thesurface modifier for use in the present invention can be obtained.Alternatively, the doped-type metal sulfide phosphor nanoparticledispersion, containing the surface modifier for use in the presentinvention, prepared according to the above method, may be centrifuged orfiltrated, and the resulting supernatant or filtrate may be subject toultrafiltration, so that a colloidal dispersion of metal sulfidephosphor nanoparticles free from salt byproducts and the excessiveamount of the surface modifier for use in the present invention can beobtained. When the metal sulfide phosphor nanoparticles are produced inthe form of a fine powder, the above dispersion or a dispersionsynthesized by a reverse micelle method as described later is preferablysubjected to freeze drying or vacuum drying at a low temperature of, forexample, 50° C. or lower. In particular, the fine powder produced byfreeze-drying is preferred because it can easily be dispersed again in asolvent.

The concentration of the nanoparticles in the dispersion of thedoped-type metal sulfide phosphor nanoparticles of the present inventionis preferably from 0.05 mM to 1,000 mM, more preferably from 0.1 mM to500 mM.

In the above coprecipitation method, the concentration of the metalsulfide in the reaction liquid for producing nanoparticles may be set ina relatively wide range from 0.1 mM to 1,000 mM, but is preferably setin the range from 0.5 mM to 500 mM. The metal sulfide phosphornanoparticles are preferably synthesized under the conditions that thetotal number of moles of the doping metal ion and the matrix metal ionis greater by at least 1%, preferably 2 to 40%, than the number of molesof the sulfide ion. In this case, there is provided an advantage thatthe zeta potential of the resulting metal sulfide can be positive sothat the surface modifier for use in the present invention can be easilyadsorbed on it.

(2) Reverse Micelle Method

To a reverse micelle solution (I) of a mixture of an aqueous solution ofa metal salt (e.g. zinc acetate and manganese acetate) and a non-watersoluble organic solvent (hereinafter also referred to as “hydrophobicorganic solvent”) containing a surfactant, is added another reversemicelle solution (II) of a mixture of an aqueous solution of a sulfide(a sulfide, for example, of an alkali metal or ammonia) and a non-watersoluble organic solvent containing a surfactant, to form doped-typemetal sulfide phosphor nanoparticles. The reaction temperature isgenerally from 0 to 90° C., preferably from 3 to 60° C., and thereaction time is generally from one minute to 60 minutes, preferablyfrom three minutes to 30 minutes. In each of the reverse micellesolutions (I) and (II), the mass ratio of water to the surfactant(water/surfactant) is generally 20 or less, preferably from 0.1 to 10.In the reaction liquid for forming nanoparticles, the concentration ofthe metal sulfide is generally from 0.1 mM to 100 mM, preferably from0.5 mM to 50 mM. In this method, the metal sulfide phosphornanoparticles are also preferably synthesized under the conditions thatthe total number of moles of the doping metal ion and the matrix metalion is greater by at least 1%, preferably 2 to 40%, than the number ofmoles of the sulfide ion.

After the doped-type metal sulfide phosphor nanoparticles are formed, acertain process is preferably performed which includes the steps of:adding the surface modifier for use in the present invention (ifnecessary, the surface modifier may be added in the form of a waterand/or primary alcohol solution); precipitating the phosphornanoparticles; and adding a good solvent for the surface modifier foruse in the present invention to the resultant precipitate, tore-disperse the precipitate, for the purpose of washing and dispersingthe precipitate.

As the surfactant, an oil-soluble surfactant may be used. Specificexamples of the oil-soluble surfactant include sulfonate types (e.g.,sodium bis(2-ethylhexyl)sulfosuccinate), quaternary ammonium salt types(e.g., cetyltrimethylammonium bromide), and ether types (e.g.,pentaethylene glycol dodecyl ether).

Preferable examples of the water-insoluble organic solvent for use indissolving the surfactant include alkanes and ethers. The alkanes arepreferably those having 7 to 12 carbon atoms. Specifically, heptane,octane, nonane, decane, iso-octane, undecane, and dodecane arepreferable. The ethers are preferably diethyl ether, dipropyl ether, anddibutyl ether. The amount of the surfactant in the water-insolubleorganic solvent is preferably 20 to 200 g/L. Further, in the reversemicelle solution (I) and the reverse micelle solution (II), thesurfactant to be used may be the same or different form each other, andthe mass ratio range of water to the surfactant may be the same as ordifferent.

Because the phosphor nanoparticle formation reaction infers greatinfluence on the monodispersibility of the distribution of particlediameter, it is preferable to run the reaction with stirring at a rateas high as possible. A preferable stirring apparatus is a stirrer havinghigh shearing force. In detail, the apparatus is such a stirrer having astructure, in which the stirring blade basically has a turbine-type orpaddle-type structure, also a sharp edge is attached to a position whereit is in contact with the end of the blade or with the blade, and theblade is rotated using a motor. Specifically, as the stirrer, Dissolver(manufactured by Tokushu Kika Kogyo Co., Ltd.), Omni Mixer (manufacturedby Yamato Scientific Co., Ltd.), and Homogenizer (manufactured by SMT)are useful. The use of each of these apparatuses makes it possible tosynthesize a monodispersed nanoparticle in the form of a stabledispersion.

[4] Fluorescent Label Material

The nano phosphor particles having the coating of the surface modifierrepresented by formula [1] may also be coupled to a specific affinitymolecule, such as nucleic acids (e.g. nucleic acid monomers,oligonucleotides, and the like), antibodies (e.g. monoclonal antibodies,any other proteins and amino acids), and polysaccharides, via a terminalreactive group of the surface modifier, such as an amino group and acarboxyl group, by, for example, an amidation reaction for forming apeptide bond. The product coupled to the affinity molecule may beallowed to bind to a specific biomolecule, to serve as a fluorescentlabel material. When such a fluorescent label material is used, thebiomolecule or the like may be a native material (e.g. in vivo) or aforeign material (e.g. in vitro).

The amidation reaction may be a condensation reaction of a carboxylgroup or any derivative group thereof (such as an ester group, an acidanhydride group, and an acid halide group) with an amino group. The acidanhydride or the acid halide is preferably used together with a base. Inthe reaction using a methyl or ethyl ester of the carboxylic acid,heating or reducing pressure is preferably performed for the purpose ofremoving an alcohol produced. In the case where direct amidation of thecarboxyl group is carried out, an amidation reaction-acceleratingsubstance/agent, which includes an amidation reagent such as DCC,Morpho-CDI and WSC, a condensation additive such as HBT, and an activeester agent such as N-hydroxyphthalimide, p-nitrophenyltrifluoroacetate, and 2,4,5-trichlorophenol, may be allowed to coexistor react in advance. In the amidation process, any one of the carboxylgroup and the amino group of the affinity molecule to be coupled byamidation is preferably protected with a suitable blocking groupaccording to a usual method, and then deprotected after the reaction.

The nanoparticle phosphor coupled to the affinity molecule by theamidation reaction, may be washed and purified in a usual manner such asgel filtration, and then dispersed in water and/or a hydrophilic solvent(preferably methanol, ethanol, isopropanol, or 2-ethoxyethanol) beforeuse. In such a dispersion, the nanoparticle phosphor may have anyconcentration that can vary depending on fluorescent intensity and isnot particularly limited, but it preferably has a concentration of 10⁻¹M to 10⁻¹⁵ M, more preferably a concentration of 10⁻² M to 10⁻¹⁰ M.

The presence of the coating of the modifier molecule on the surface ofthe phosphor nanoparticles may be confirmed, by identifying a constantdistance between the particles in the observation with high-resolutionTEM such as FE-TEM, and by chemical analysis.

According to the present invention, a doped-type metal sulfide phosphornanoparticle having good dispersibility, a dispersion thereof, andmethods for producing them, can be provided. In particular, according tothe present invention, a doped-type metal sulfide phosphor nanoparticlethat has high sensitivity, uniform luminescent properties, safety, andless influence on the environment, and that can easily befunctionalized; a dispersion thereof, and methods for producing them,can be provided. Further, according to the present invention, afluorescent-labeling material that allows high-sensitivity, high-speeddetection of a specific site of a living organism, a certain substancein plasma, or the like, in a simple system or apparatus, can beprovided.

The doped-type metal sulfide phosphor nanoparticle of the presentinvention can form a stable water-based colloidal dispersion or a stablehydrophobic organic solvent-based colloidal dispersion. The dispersionof the surface modifier-covered, doped-type metal sulfide phosphornanoparticle according to the present invention, may be allowed to reactwith a protein such as an antibody (to form, for example, a peptidebond), such that it can function as a marker (a fluorescent-labelingmaterial) for a specific substance in a living organism, or the like.

The present invention will be described in more detail based on examplesgiven below, but the invention is not meant to be limited by these.

EXAMPLES Example 1

In 60 ml of water, were dissolved 15 g of zinc acetate 2 hydrate and 0.5g of manganese acetate 4 hydrate, to prepare a solution, which isdesignated as Solution 1. In 60 ml of water, was dissolved 12.4 g ofsodium sulfide 9 hydrate, to prepare a solution, which is designated asSolution 2. The resultant Solutions 1 and 2 were simultaneously added to80 ml of water in a 300-ml beaker at a speed of 10 ml/minute, while thewater was vigorously stirred. Thus, a white precipitate was produced,and it showed a strong orange fluorescence when irradiated with 302 nmultraviolet light. To the product, was added 20 g of2-mercaptopropylamine hydrochloride, followed by stirring for 30minutes. The resultant mixture was then allowed to stand, and theresultant supernatant was filtrated with a 0.2-μm filter. The filtrateshowed a strong orange fluorescence when irradiated with 302 nmultraviolet light. The filtrate was ultrafiltrated using a filter with amolecular-weight cutoff of 10,000. Water was further added thereto, andwashing and ultrafiltration were repeated, to remove the salts and theexcessive amount of the 2-mercaptopropylamine and to purify theresultant colloidal dispersion of ZnS:Mn. The colloidal dispersion wasfiltrated with a 0.2-μm filter, and the filtrate (designated asSample 1) was measured for fluorescence spectrum at an excitationwavelength of 306 nm. As a result, an orange luminescence having amaximum at about 590 nm was observed. The concentration of thenanoparticles in the filtrate was 16 mM. The average crystallite size ofthe produced ZnS:Mn was determined to be 2.8 nm, by XRD measurement. Theparticle size distribution of the phosphor nanoparticles was 15% interms of coefficient of variation.

Example 2

Samples 2 to 5 were prepared in the same manner as Sample 1 in Example1, except that, although the molar ratio between the zinc acetate 2hydrate and the manganese acetate 4 hydrate was the same as Sample 1,the total number of moles of the acetates was changed relative to thenumber of moles of the sodium sulfide, as shown in Table 1 below. Thefluorescence spectrum of each sample was measured. The relativeintensity of the luminescence is shown in Table 1.

Example 3

Samples 6 to 11 were prepared in the same manner as Sample 1 in Example1, except that a different kind of surface modifier was used, as shownin Table 1. The flouorescence spectrum of each sample was measured. Therelative intensity of the luminescence is shown in Table 1. TABLE 1 Sam-Relative ple Molar luminescence No. Surface modifier ratio*¹ intensity*²1 2-Mercaptopropylamine hydrochloride 1.11 +++ 2 2-Mercaptopropylaminehydrochloride 1.20 +++ 3 2-Mercaptopropylamine hydrochloride 1.05 +++ 42-Mercaptopropylamine hydrochloride 1.00 ++ 5 2-Mercaptopropylaminehydrochloride 0.90 + 6 2-Mercaptoethylamine hydrochloride 1.11 +++ 73-Mercapto-n-butylamine hydrochloride 1.11 ++ 8 2-Mercapto-t-butylamine½ sulfate 1.11 +++ 9 3-Mercaptopropylamine hydrochloride 1.11 +++ 102-Mercaptonicotinic acid 1.11 ± 11 Butylamine hydrochloride 1.11 ±*¹The ratio of the total number of moles of the Zn and Mn salts to thenumber of moles of sodium sulfide*²+++ Very high intensity, ++ high intensity, + medium intensity, ±almost no fluorescence was observed

In Table 1, Samples 1 to 9 (Examples according to the present invention)each showed excellent results, contrary to those of Samples 10 and 11(Comparative Examples). It has been found that the luminescenceintensity of each of Samples 1 to 3 and 6 to 9, in which the totalnumber of moles of the metal salts (the zinc salt and the manganesesalt) was larger than the number of moles of sodium sulfide, was higherthan that of Sample 4 or 5 (Examples which did not satisfy therequirements as stated in the above item (14)). It has also been foundthat the surface modifier for use in the present invention can producequite high luminescence intensity. Comparative Example 1 (ComparativeExample to the invention according to the above item (11)) A sample wasprepared in the same manner as in Example 1, except that2-mercaptoethylamine had been added to the water in advance, to whichthe Solutions 1 and 2 were added simultaneously. As a result, theluminescence intensity was significantly reduced (luminescenceintensity: ±). It has been found that the surface modifier for use inthe present invention is preferably added after the formation of thenanoparticle phosphor of ZnS:Mn.

Example 4

In 60 ml of water, was dissolved 6.46 g of zinc chloride, to prepare asolution, which is designated as Solution 3. Separately, in 80 ml ofwater, was dissolved 42 mg of copper chloride, to prepare a solution,which is designated as Solution 4. Further, in 60 ml of water, wasdissolved 10.4 g of sodium sulfide 9 hydrate, to prepare a solution,which is designated as Solution 5. To Solution 4 vigorously stirred, wasadded 50 μl of Solution 5. Solution 3 and the remainder of Solution 5were simultaneously added thereto, at a rate of 10 ml/minute. After theaddition was completed, the mixture was further stirred for 10 minutes.Then, 200 ml of a 10-mass % aqueous solution of 2-mercaptopropylaminehydrochloride, which is a surface modifier for use in the presentinvention, was added thereto, followed by stirring for 10 minutes andthen allowing to stand for 10 days. The resulting supernatant wasfiltrated with a 0.2-μm filter, and the filtrate was measured forfluorescence spectrum at an excitation wavelength of 312 nm. As aresult, a blue-green luminescence (luminescence intensity: ++) having amaximum at about 490 nm was observed. The particle size distribution ofthe phosphor nanoparticles was 21% in terms of coefficient of variation.

Comparative Example 2 (Comparative Example to the Invention According tothe Above Item (14))

A sample was prepared in the same manner as in Example 4, except thatthe amount of the sodium sulfide 9 hydrate to be used was increased to12.7 g, and that the number of moles of sodium sulfide was changed suchthat it would be greater by 10% than the number of moles of the metalsalts. As a result, the luminescence intensity was reduced (luminescenceintensity: +). It has been found that the total number of moles of themetal salts is also preferably greater than the number of moles ofsodium sulfide, in the case of the nanoparticle phosphor of ZnS:Cu.

Example 5

To 150 ml of n-heptane, were added 21.3 g of sodiumbis(2-ethylhexyl)sulfosuccinate (AOT) and 5.2 g of water. They weremixed and stirred at 3,000 rpm for 10 minutes with a homogenizer, toprepare a micelle solution, which is designated as Micelle solution I.Was weighed 133 mg of sodium sulfide 9 hydrate, and this was then addedto and mixed with 20 ml of the Micelle solution I, to prepare asolution, which is designated as Solution A.

Were weighed 101 mg of zinc acetate and 13 mg of manganese acetate 4hydrate, and they were then added to and mixed with 80 ml of the Micellesolution I, to prepare a solution, which is designated as Solution B.

Using a homogenizer, Solution B was stirred at 3,000 rpm for 10 minutes,and Solution A was added thereto, followed by stirring for 10 minutes,to form a mixture, in which the total number of moles of the metal saltswas 1.1 times the number of moles of sodium sulfide. Thus, a cleardispersion of ZnS:Mn colloid was formed. To the dispersion, was added300 ml of a 5%-methanol solution of 3-mercaptopropylamine nitrate,followed by gentle stirring and then allowing to stand. The resultingsupernatant was removed by decantation, and 300 ml of methanol was addedto the residue, followed by gentle stirring and then allowing to stand.The supernatant was removed by decantation, and 50 ml of water was addedto the precipitate. Thus, an aqueous colloidal dispersion of ZnS:Mnwhose surface was modified with 3-mercaptopropylamine, was obtained.

The dispersion was measured for fluorescence spectrum at an excitationwavelength of 325 nm. As a result, an orange luminescence having amaximum at about 590 nm was observed (luminescence intensity: +++). Theconcentration of the nanoparticles in the filtrate was 7 mM. The averagecrystallite size of the thus-produced ZnS:Mn was determined to be 4.2nm, by XRD measurement. The particle size distribution of the phosphornanoparticles was 14% in terms of coefficient of variation.

Comparative Example 3 (Comparative Example to the Invention According tothe Above Item (14))

An aqueous colloidal dispersion of ZnS:Mn surface-modified with3-mercaptopropylamine, was prepared in the same manner as in Example 5,except that the amounts of the zinc acetate and the manganese acetate 4hydrate to be used in Solution B were changed to 87 mg and 11 mg,respectively, and that the total number of moles of the metal salts waschanged to be 0.94 times the number of moles of sodium sulfide. As aresult, the fluorescence intensity was reduced (luminescence intensity:+). It has been found that the total number of moles of the metal saltsis preferably greater than the number of moles of sodium sulfide also inthe case where a reverse micelle method is used for the synthesis ofZnS:Mn phosphor nanoparticles.

Example 6

A sample was prepared in the same manner as in Example 5, except that a5%-methanol solution of 18-mercaptooleylamine was used in washing inplace of the solution of 3-mercaptopropylamine, and then 50 ml oftoluene was added thereto. Thus, a toluene colloidal dispersion ofZnS:Mn whose surface was modified with 18-mercaptooleylamine, wasobtained. The luminescence performance of this dispersion was the sameas that of the aqueous colloidal dispersion in Example 5.

It has been found that the doped-type metal sulfide phosphornanoparticles synthesized according to the reverse micelle method, canbe made to be dispersible in a hydrophobic organic solvent, as well as awater-based solvent, by using the surface modifier for use in thepresent invention properly selected among those having different carbonatoms (namely having different solubility parameters).

Example 7

In 600 ml of water, were dissolved 11 g of zinc acetate 2 hydrate and0.37 g of manganese acetate 4 hydrate, to prepare a solution, which isdesignated as Solution 1. To 15 g of7-hydroxy-5-methyl-1,3,4-triazaindolizine, was added 680 ml of water,followed by heating at 80° C. to dissolve the compound in the water andfurther adding 120 ml of Solution 1 thereto, to prepare a solution,which is designated as Solution 2. Separately, in 600 ml of water, wasdissolved 12.4 g of sodium sulfide 9 hydrate, to prepare a solution,which is designated as Solution 3. While Solution 2 was kept at 80° C.and vigorously stirred, the remainder of Solution 1 and the aboveSolution 3 were simultaneously added thereto, at a rate of 8 ml/minuteand at a rate of 10 ml/minute, respectively. Thus, a translucentcolloidal dispersion was obtained. To 50 ml of the colloidal dispersion,was added 6.5 ml of a 0.1-M solution of 2-mercaptopropylaminehydrochloride, followed by mixing them. The resulting colloidaldispersion showed a strong orange fluorescence (luminescence intensity:+++) having a maximum at about 590 nm when irradiated with 330-nmultraviolet light. XRD measurement revealed that ZnS:Mn nanoparticleswere produced with an average crystallite size of 3 nm.

Example 8

To the colloidal dispersion of the ZnS:Mn nanoparticle phosphor preparedin Example 7, was added NaHCO₃ such that the concentration would be 0.1%by mass, and the pH was adjusted to 7.5. Thereto, was added a 1-mass %aqueous solution of sulfosuccinimidyl:D-biotin (manufactured by DOJINDOLABORATORIES) as a biotin labeling agent, to carry out an amidationreaction. The reaction product was purified by gel filtration, to give a10-M aqueous dispersion of ZnS:Mn nanoparticle phosphor to which biotinwas coupled as a functional molecule. Using this dispersion, avidin wasfluorescently labeled, to detect.

Example 9

In 60 ml of water, were dissolved 15 g of zinc acetate 2 hydrate and 0.5g of manganese acetate 4 hydrate, to prepare a solution, which isdesignated as Solution 1. In 60 ml of water, was dissolved 12.4 g ofsodium sulfide 9 hydrate, to prepare a solution, which is designated asSolution 2. The resultant Solutions 1 and 2 were simultaneously added to80 ml of water in a 300-ml beaker at a speed of 10 ml/minute, while thewater was vigorously stirred. Thus, a white precipitate was produced,and it showed a strong orange fluorescence when irradiated with 302nmultraviolet light. To the product, was added 40 ml of2-mercaptopropionic acid, followed by stirring for 30 minutes. Theresultant mixture was then allowed to stand, and the resultantsupernatant was filtrated with a 0.2-μm filter. The filtrate showed astrong orange fluorescence when irradiated with 302 nm ultravioletlight. The filtrate was ultrafiltrated using a filter with amolecular-weight cutoff of 10,000. Water was further added thereto, andwashing and ultrafiltration were repeated, to remove the salts and theexcessive amount of the 2-mercaptopropionic acid and to purify theresultant colloidal dispersion of ZnS:Mn. The colloidal dispersion wasfiltrated with a 0.2-μm filter, and the filtrate (designated as Sample1a) was measured for fluorescence spectrum at an excitation wavelengthof 306 nm. As a result, an orange luminescence having a maximum at about590 nm was observed. The concentration of the nanoparticles in thefiltrate was 20 mM. The average crystallite size of the produced ZnS:Mnwas determined to be 2.8 nm, by XRD measurement. The particle sizedistribution of the phosphor nanoparticles was 15% in terms ofcoefficient of variation.

Example 10

Samples 2a to 5a were prepared in the same manner as Sample 1a inExample 9, except that, although the molar ratio between the zincacetate 2 hydrate and the manganese acetate 4 hydrate was the same asSample 1a, the total number of moles of the acetates was changedrelative to the number of moles of the sodium sulfide, as shown in Table2 below. The fluorescence spectrum of each sample was measured. Therelative intensity of the luminescence is shown in Table 2.

Example 11

Samples 6a to 12a were prepared in the same manner as Sample 1a inExample 9, except that a different kind of surface modifier was used, asshown in Table 2. The fluorescence spectrum of each sample was measured.The relative intensity of the luminescence is shown in Table 2. TABLE 2Relative Sample Molar luminescence No. Surface modifier ratio*¹intensity*² 1a 2-Mercaptopropionic acid 1.11 +++ 2a 2-Mercaptopropionicacid 1.20 +++ 3a 2-Mercaptopropionic acid 1.05 +++ 4a2-Mercaptopropionic acid 1.00 ++ 5a 2-Mercaptopropionic acid 0.90 + 6aMercaptoacetic acid 1.11 ++ 7a Thiomalic acid 1.11 +++ 8aMercaptomethacryric acid 1.11 +++ 9a Sodium 2-mercaptopropionate 1.11+++ 10a  Sodium thiomalate 1.11 +++ 11a  Succinic acid 1.11 ± 12a 2-Mercaptonicotinic acid 1.11 ±*¹The ratio of the total number of moles of the Zn and Mn salts to thenumber of moles of sodium sulfide*²+++ Very high intensity, ++ high intensity, + medium intensity, ±almost no fluorescence was observed

In Table 2, Samples 1a to 10a (Examples according to the presentinvention) each showed excellent results, contrary to those of Samples11a and 12a (Comparative Examples). It has been found that theluminescence intensity of each of Samples la to 3a and 6a to 10a, inwhich the total number of moles of the metal salts (the zinc salt andthe manganese salt) was larger than the number of moles of sodiumsulfide, was higher than that of Sample 4a or 5a (Examples which did notsatisfy the requirements as stated in the above item (14)). It has alsobeen found that the surface modifier for use in the present inventioncan produce quite high luminescence intensity.

Comparative Example 4 (Comparative Example to the Invention According tothe Above Item (11))

A sample was prepared in the same manner as in Example 9, except thatmercaptoacetic acid had been added to the water in advance, to which theSolutions 1 and 2 were added simultaneously. As a result, theluminescence intensity was significantly reduced (luminescenceintensity: ±). It has been found that the surface modifier for use inthe present invention is preferably added after the formation of thenanoparticle phosphor of ZnS:Mn.

Example 12

In 60 ml of water, was dissolved 6.46 g of zinc chloride, to prepare asolution, which is designated as Solution 3. Separately, in 80 ml ofwater, was dissolved 42 mg of copper chloride, to prepare a solution,which is designated as Solution 4. Further, in 60 ml of water, wasdissolved 10.4 g of sodium sulfide 9 hydrate, to prepare a solution,which is designated as Solution 5. To Solution 4 vigorously stirred, wasadded 50 μl of Solution 5. Solution 3 and the remainder of Solution 5were simultaneously added thereto, at a rate of 10 ml/minute. After theaddition was completed, the mixture was further stirred for 10 minutes.Then, 200 ml of a 20-mass % aqueous solution of thiomalic acid, which isa surface modifier for use in the present invention, was added thereto,followed by stirring for 10 minutes and then allowing to stand for 10days. The resulting supernatant was filtrated with a 0.2-μm filter, andthe filtrate was measured for fluorescence spectrum at an excitationwavelength of 312 nm. As a result, a blue-green luminescence(luminescence intensity: ++) having a maximum at about 490 nm wasobserved. The particle size distribution of the phosphor nanoparticleswas 23% in terms of coefficient of variation.

Comparative Example 5 (Comparative Example to the Invention According tothe Above Item (14))

A sample was prepared in the same manner as in Example 12, except thatthe amount of the sodium sulfide 9 hydrate to be used was increased to12.7 g, and that the number of moles of sodium sulfide was changed suchthat it would be greater by 10% than the number of moles of-the metalsalts. As a result, the luminescence intensity was reduced (luminescenceintensity: +). It has been found that the total number of moles of themetal salts is also preferably greater than the number of moles ofsodium sulfide, in the case of the nanoparticle phosphor of ZnS:Cu.

Example 13

To 150 ml of n-heptane, were added 21.3 g of sodiumbis(2-ethylhexyl)sulfosuccinate (AOT) and 5.2 g of water. They weremixed and stirred at 3,000 rpm for 10 minutes with a homogenizer, toprepare a micelle solution, which is designated as Micelle solution I.Was weighed 133 mg of sodium sulfide 9 hydrate, and this was then addedto and mixed with 20 ml of the Micelle solution I, to prepare asolution, which is designated as Solution A.

Were weighed 101 mg of zinc acetate and 13 mg of manganese acetate 4hydrate, and they were then added to and mixed with 80 ml of the Micellesolution I, to prepare a solution, which is designated as Solution B.

Using a homogenizer, Solution B was stirred at 3,000 rpm for 10 minutes,and Solution A was added thereto, followed by stirring for 10 minutes,to form a mixture, in which the total number of moles of the metal saltswas 1.1 times the number of moles of sodium sulfide. Thus, a cleardispersion of ZnS:Mn colloid was formed. To the dispersion, was added300 ml of a 5%-methanol solution of thiomalic acid, followed by gentlestirring and then allowing to stand. The resulting supernatant wasremoved by decantation, and 300 ml of a 5%-methanol solution ofthiomalic acid was, again, added to the residue, followed by gentlestirring and then allowing to stand. The supernatant was removed bydecantation, and 50 ml of water was added to the precipitate. Thus, anaqueous colloidal dispersion of ZnS:Mn whose surface was modified withthiomalic acid, was obtained.

The dispersion was measured for fluorescence spectrum at an excitationwavelength of 325 nm. As a result, an orange luminescence having amaximum at about 590 nm was observed (luminescence intensity: +++). Theconcentration of the nanoparticles in the filtrate was 10 mM. Theaverage crystallite size of the thus-produced ZnS:Mn was determined tobe 4.5 nm, by XRD measurement. The particle size distribution of thephosphor nanoparticles was 12% in terms of coefficient of variation.

Comparative Example 6 (Comparative Example to the Invention According tothe Above Item (14))

An aqueous colloidal dispersion of ZnS:Mn surface-modified withthiomalic acid, was prepared in the same manner as in Example 13, exceptthat the amounts of the zinc acetate and the manganese acetate 4 hydrateto be used in Solution B were changed to 87 mg and 11 mg, respectively,and that the total number of moles of the metal salts was changed to be0.94 times the number of moles of sodium sulfide. As a result, thefluorescence intensity was reduced (luminescence intensity: +). It hasbeen found that the total number of moles of the metal salts ispreferably greater than the number of moles of sodium sulfide also inthe case where a reverse micelle method is used for the synthesis ofZnS:Mn phosphor nanoparticles.

Comparative Example 7

A sample was prepared in the same manner as in Example 13, except that a5% methanol solution of succinic acid was used in washing in place ofthiomalic acid, and then 50 ml of water was added thereto. The resultingaqueous dispersion of ZnS:Mn colloid was unstable and sufferedsedimentation immediately. It has been found that the doped-type metalsulfide phosphor nanoparticle produced with the surface modifier for usein the present invention, is excellent in stability as a dispersion.

Example 14

A sample was prepared in the same manner as in Example 13, except that a5%-methanol solution of 11-mercaptoundecanoic acid was used in washingin place of the solution of thiomalic acid, and then 50 ml of toluenewas added thereto. Thus, a toluene colloidal dispersion of ZnS:Mn whosesurface was modified with 11-mercaptoundecanoic acid, was obtained. Theluminescence performance of this dispersion was the same as that of theaqueous colloidal dispersion in Example 13.

It has been found that the doped-type metal sulfide phosphornanoparticles synthesized according to the reverse micelle method, canbe made to be dispersible in a hydrophobic organic solvent, as well as awater-based solvent, by using the surface modifier for use in thepresent invention properly selected among those having different carbonatoms (namely having different solubility parameters).

Having described our invention as related to the present embodiments, itis our intention that the invention not be limited by any of the detailsof the description, unless otherwise specified, but rather be construedbroadly within its spirit and scope as set out in the accompanyingclaims.

1. A doped-type metal sulfide phosphor nanoparticle dispersion,comprising a doped-type metal sulfide phosphor nanoparticle dispersed inwater and/or a hydrophilic solvent, wherein the doped-type metal sulfidephosphor nanoparticle comprises a surface that is modified with asurface modifier, the surface modifier being a compound represented byformula [I]:HS-L-W   Formula [I] wherein L represents a divalent linking group; andW represents COOM or NH₂, in which M represents a hydrogen atom, analkali metal atom, or NX₄, in which X represents a hydrogen atom or analkyl group.
 2. The doped-type metal sulfide phosphor nanoparticledispersion according to claim 1, further comprising anitrogen-containing heterocyclic compound in the dispersion.
 3. A methodof producing a dispersion of a doped-type metal sulfide phosphornanoparticle whose surface is modified with a surface modifier,comprising the steps of: carrying out a reaction of a doping metal ionand a matrix metal ion, with a sulfide ion, in water and/or ahydrophilic solvent by a coprecipitation method; and adding thereto asurface modifier comprising a compound represented by formula [I]:HS-L-W   Formula [I] wherein L represents a divalent linking group; andW represents COOM or NH₂, in which M represents a hydrogen atom, analkali metal atom, or NX₄, in which X represents a hydrogen atom or analkyl group.
 4. The method of producing a dispersion of a doped-typemetal sulfide phosphor nanoparticle according to claim 3, wherein thereaction is carried out under conditions that the total number of molesof the doping metal ion and the matrix metal ion is greater than thenumber of moles of the sulfide ion.
 5. The method of producing adispersion of a doped-type metal sulfide phosphor nanoparticle accordingto claim 3, comprising the step of: performing purification bycentrifugal separation.
 6. The method of producing a dispersion of adoped-type metal sulfide phosphor nanoparticle according to claim 3,comprising the step of: performing purification by ultrafiltration.
 7. Amethod of producing a dispersion of a doped-type metal sulfide phosphornanoparticle, comprising the steps of: carrying out a reaction of adoping metal ion and a matrix metal ion, with a sulfide ion, in thepresence of nitrogen-containing heterocyclic compound in water and/or ahydrophilic solvent; and adding thereto a compound represented byformula [I]:HS-L-W   Formula [I] wherein L represents a divalent linking group; andW represents COOM or NH₂, in which M represents a hydrogen atom, analkali metal atom, or NX₄, in which X represents a hydrogen atom or analkyl group.
 8. The method of producing a dispersion of a doped-typemetal sulfide phosphor nanoparticle according to claim 7, wherein thereaction is carried out under conditions that the total number of molesof the doping metal ion and the matrix metal ion is greater than thenumber of moles of the sulfide ion.
 9. The method of producing adispersion of a doped-type metal sulfide phosphor nanoparticle accordingto claim 7, comprising the step of: performing purification bycentrifugal separation.
 10. The method of producing a dispersion of adoped-type metal sulfide phosphor nanoparticle according to claim 7,comprising the step of: performing purification by ultrafiltration.